EvidenceBModerateGood evidence in people with one real weakness. New studies could change the answer.
Yes, GLP-1 drugs reduce lean mass along with fat, about a quarter of the weight lost. Whether that means weaker muscles in daily life hasn't been tested well.
Who it's for
People losing weight on these drugs; older or frail adults need more care.
What to expect
About 1 kg less lean mass than comparison groups, about 25% of weight lost.
Watch out for
Lean mass includes more than muscle, and strength was rarely measured.
GLP-1 drugs lead to a small loss of lean mass
Each dot is the average change in lean mass versus controls, with a line showing the range of likely values.
← WorseBetter →
No difference
Network meta-analysis of trials−0.86 (−1.3 to −0.42)Clear worsening
Meta-analysis of 19 trials−1.02 (−1.46 to −0.57)Clear worsening
A review that pooled 22 trials (2,258 adults) found GLP-1 drugs cut lean mass by about 0.9 kg more than comparison groups. Lean mass made up about 25% of total weight lost. As a share of body weight, lean mass did not change1Meta-analysis · 2025 · 2,258 peopleEffect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis.Potent GLP-1 RAs, such as tirzepatide and semaglutide, demonstrate greater overall weight loss but are associated with a significant reduction in lean mass.Metabolism. A second review of 19 trials found a similar loss of about 1 kg2Meta-analysis · 2025Characterizing body composition modifying effects of a glucagon-like peptide 1 receptor-based agonist: A meta-analysis.Compared with the controls, GLP-1 receptor-based agonist users experienced greater reductions in fat body mass, with body shaping effects in terms of both subcutaneous fat mass and visceral fat mass. Although greater reductions in lean body mass were also observed in GLP-1 receptor-based agonist users, the changes in…Diabetes Obes Metab.
Tirzepatide and semaglutide gave the most weight loss and were among the weakest at preserving lean mass. Liraglutide was the only drug without a significant lean mass drop1Meta-analysis · 2025 · 2,258 peopleEffect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis.Potent GLP-1 RAs, such as tirzepatide and semaglutide, demonstrate greater overall weight loss but are associated with a significant reduction in lean mass.Metabolism. One small 16-week liraglutide trial also saw no lean mass loss, but it was tiny (40 people)10Randomized trial · 2020GLP-1 Analog Modulates Appetite, Taste Preference, Gut Hormones, and Regional Body Fat Stores in Adults with Obesity.Liraglutide 3 mg SQ modulates appetite, taste preference, gut hormones, and regional body fat stores in adults with obesity without reduction in lean body mass.J Clin Endocrinol Metab.
A review of 38 publications (1,735 adults) found lean mass loss under 20% of total weight lost. In people with type 2 diabetes the drop could be down to chance3Meta-analysis · 2025 · 1,735 peopleHow do glucagon-like Peptide-1 receptor agonists affect measures of muscle mass in individuals with, and without, type 2 diabetes: A systematic review and meta-analysis.In both populations, the reduction in measures of MM accounted for less than 20% of the total weight reduction. These findings provide some clarity to clinicians that use GLP1RAs to manage individuals with T2DM and/or obesity, however, further more detailed analysis of the impact of these medications on functional…Obes Rev. For semaglutide, lean mass made up almost 0% to 40% of weight lost across six studies4Systematic review · 2024A systematic review of the effect of semaglutide on lean mass: insights from clinical trials.Semaglutide displays potential for weight loss primarily through fat mass reduction. However, concerns arise from notable reductions in lean mass, especially in trials with a larger number of patients.Expert Opin Pharmacother.
A pooled analysis of 20 trials found lean mass made up 35% of weight lost on semaglutide, 25% on tirzepatide and 27% on liraglutide. Lifestyle weight loss was similar at 26%, and adding resistance training cut it to about 18%6Meta-analysis · 2026 · 782 peopleLean Mass Changes With Incretin Therapy Versus Lifestyle Intervention: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.Lean mass loss during significant weight reduction is substantial, and the proportion of weight lost as lean mass is broadly comparable between incretin-based pharmacotherapy and lifestyle interventions. Muscle mass can be significantly preserved by integrating resistance training, adequate protein intake, and body…Diabetes Obes Metab. Dieting alone also costs muscle, so the drugs are not unique here. These figures compare groups, so one person's loss depends on their starting point.
In an MRI study of 246 adults with type 2 diabetes, thigh muscle volume fell about 0.64 L after 52 weeks on tirzepatide. That fits the weight lost. Muscle fat also fell5Randomized trial · 2025 · 502 peopleTirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial.In the SURPASS-3 MRI substudy, in the context of significant improvements in bodyweight and fat distribution, tirzepatide treatment was associated with potentially favourable changes in muscle fat infiltration and reductions in muscle volume broadly in accordance with the general association between changes in muscle…Lancet Diabetes Endocrinol. A review judged these changes likely adaptive, though older or prefrail people may risk sarcopenia (muscle weakness with age)9Review · 2024Muscle Mass and Glucagon-Like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss?Several pharmacologic treatments to maintain or improve muscle mass designed in combination with GLP-1-based therapies are under development. For future development of GLP-1-based therapies (and other therapies) designed for weight loss, as well as for patient-centered treatment optimization, the introduction of more…Circulation.
In a 102-person trial, adding an experimental antibody (apitegromab, not approved) to tirzepatide kept 1.9 kg more lean mass over 24 weeks7Randomized trial · 2026 · 102 peopleApitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial.ClinicalTrials. gov identifier: NCT06445075 .Nat Med. Other muscle-preserving drugs are being tested15Registered trial · 2022Safety and Efficacy of Bimagrumab and Semaglutide in Adults Who Are Overweight or ObeseClinicalTrials.gov.
Key studies
Study
Who
What it found
Review of 22 trials, 20251Meta-analysis · 2025 · 2,258 peopleEffect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis.Potent GLP-1 RAs, such as tirzepatide and semaglutide, demonstrate greater overall weight loss but are associated with a significant reduction in lean mass.Metabolism
2,258 adults with overweight or diabetes
Lean mass loss was about 25% of weight lost
Review of 20 trials, 20266Meta-analysis · 2026 · 782 peopleLean Mass Changes With Incretin Therapy Versus Lifestyle Intervention: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.Lean mass loss during significant weight reduction is substantial, and the proportion of weight lost as lean mass is broadly comparable between incretin-based pharmacotherapy and lifestyle interventions. Muscle mass can be significantly preserved by integrating resistance training, adequate protein intake, and body…Diabetes Obes Metab
Adults with overweight or obesity
Lean share similar to lifestyle weight loss; training lowered it
Review of 38 publications, 20253Meta-analysis · 2025 · 1,735 peopleHow do glucagon-like Peptide-1 receptor agonists affect measures of muscle mass in individuals with, and without, type 2 diabetes: A systematic review and meta-analysis.In both populations, the reduction in measures of MM accounted for less than 20% of the total weight reduction. These findings provide some clarity to clinicians that use GLP1RAs to manage individuals with T2DM and/or obesity, however, further more detailed analysis of the impact of these medications on functional…Obes Rev
1,735 adults, mean age over 40
Lean mass loss was under 20% of weight lost
Trial MRI analysis, 20255Randomized trial · 2025 · 502 peopleTirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial.In the SURPASS-3 MRI substudy, in the context of significant improvements in bodyweight and fat distribution, tirzepatide treatment was associated with potentially favourable changes in muscle fat infiltration and reductions in muscle volume broadly in accordance with the general association between changes in muscle…Lancet Diabetes Endocrinol
246 adults with type 2 diabetes
Thigh muscle volume fell 0.64 L on tirzepatide at 52 weeks
Trial, 20267Randomized trial · 2026 · 102 peopleApitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial.ClinicalTrials. gov identifier: NCT06445075 .Nat Med
102 adults on tirzepatide
Apitegromab kept 1.9 kg more lean mass
Safety
Semaglutide carries a boxed warning about thyroid tumors seen in rodents, and warnings for pancreatitis, gallbladder problems and kidney injury. Common side effects are nausea, diarrhea and vomiting12Guideline · 2024FDA Approves First Treatment to Reduce Risk of Serious Heart Problems Specifically in Adults with Obesity or OverweightIn the placebo-controlled trial behind the approval, over 17,600 participants were randomly assigned to semaglutide or placebo on top of standard care. Major adverse cardiovascular events (cardiovascular death, heart attack and stroke) occurred in 6.5% of those on semaglutide and 8% of those on placebo.US Food and Drug Administration,13Guideline · 2026Semaglutide: FDA drug label (prescribing information)Warnings and precautions: Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to anaphylaxis with RYBELSUS or OZEMPIC tablets. 5.8 Acute Gallbladder Disease Acute events of gallbladder disease such as…US Food and Drug Administration. Compounded versions are not FDA approved, and dosing errors have been reported11Guideline · 2026FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight LossHowever, compounded drugs are not FDA approved. This means the agency does not review compounded drugs for safety, effectiveness or quality before they are marketed.US Food and Drug Administration. The trials tested the approved products.
What we don't know
Whether the lean mass lost weakens strength or movement, since most studies used scans, not strength tests.
Whether older or frail people lose function, and whether resistance training and protein protect muscle on these drugs.
Written by AI from the studies listed, without review by a clinician, and graded with the GRADE method. It can be wrong, so check the studies it cites. Education, not medical advice.